It is planned to study the biochemical mechanisms underlying the compositional and ultrastructural alterations which result in increased cell size in hearts subjected to a variety of stresses known to cause hypertrophy. Protein synthesis and protein synthetic mechanisms will be studied in isolated rat hearts subjected to short periods of hypoxia and to pressure overloads, and in adult rabbit hearts subjected to afterload due to aortic or pulmonary artery banding. In the isolated rat heart, varying degrees of hypoxia will be utilized to determine the maximum effect on protein synthesis, specific proteins which are produced with specific effects on alteration of membrane permeability and intracellular amino acid pool size, and ultrastructural alterations. In addition to hypoxia, certain metabolites will be tested to determine their effect on initiation of protein synthesis. Comparison will be made between the protein synthetic pattern during initiation of hypertropy with that which occurs during continuation of the process and development of myocardial failure.